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Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades, their relatively poor capacity to stimulate immune responses, especially cellular immune responses, has limited their application. Here, we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and adjuvants. Meanwhile, a programmed death-ligand 1 (PD-L1) inhibitor, JQ-1, was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells (APCs) upon vaccination, thereby augmenting its antitumor efficacy. The fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells (BMDCs) in vitro. Following subcutaneous vaccination, the nanovaccines efficiently drained to the tumor-draining lymph nodes (TDLNs), and significantly inhibited PD-L1 expression of both dendritic cells (DCs) and macrophages within the TDLNs and tumors. As a result, the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse model. In summary, the fabricated cell membrane-based fusogenic liposomes offer a safe, effective, and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: B-cells can contribute to the suppression or progression of the tumor growth through the secretion of various cytokines. In this study, the relevance of B-cell cytokine production to the outcome variables in patients having squamous cell carcinoma (SCC) of the head and neck was studied. Materials and Methods: Thirty-six draining lymph nodes from untreated patients with tongue and larynx SCC were stimulated with CpG, recombinant CD40L and phorbol-12-myristate-13-acetate/ionomycin and analyzed by flow cytometry for the frequency of B-cell subsets based on interleukin (IL)-10 and tumor necrosis factor-alpha (TNF-α) cytokine production. Results: It was indicated that patients with uninvolved lymph nodes and low stage of the disease had an increased percentage of TNF-α+ CD19+ B-cells (p=0.006 and p=0.041, respectively), whereas the frequency of IL-10+ CD19+ B-cells showed an increasing trend in tumor-draining lymph nodes (TDLNs) of patients with grade 2+3 compared to grade 1 (p=0.054). Conclusion: Collectively, TNF-α-producing B-cells in TDLNs has been reported to be associated with good prognosticators in patients with SCC of head and neck that might have a positive role in immunity to SCC of head and neck. [ABSTRACT FROM AUTHOR]

Certain chemo-drugs could induce immunogenic cell death (ICD) activating T cell antitumor immunity while trigger indoleamine-2,3-dioxygenase (IDO) upregulation suppressing immune responses. Moreover, to achieve therapeutic efficacies on both primary tumors and tumor draining lymph nodes (TDLNs) in the meantime is still a big challenge. In this study, transfersomes functionalized with a tumor targeting, cell penetrating peptide tLyp1 (CGNKRTR) was developed to co-encapsulate doxorubicin (DOX, ICD inducer) and 1MT (IDO inhibitor). The functionalized transfersomes were complexed with microneedles (MNs) to realize co-delivery towards primary tumors and TDLNs via transdermal administration. The transfersomes were concentrated in the needles of MNs and released with needle dissolution after insertion into skin. After being internalized by cells, DOX induced tumor ICD effect to promote DCs maturation and dramatically activated cytotoxic T lymphocytes (CD8+ T), while 1MT inhibited IDO activity in DCs and reduced the immunosuppressive Tregs, thus mitigating tumor suppressive microenvironment. The nano-complexed microneedles exhibited 2.2-fold suppression in tumor growth compared with the I.V. group, which significantly enhanced anti-tumor effect. [Display omitted] [ABSTRACT FROM AUTHOR]